Skip to main content
SpringerLink
Log in

Chromosomes, Genes, and the Thyroid Gland

  • Chapter
Thyroid Disorders with Cutaneous Manifestations

  • 928 Accesses

Editorial Perspective

As molecular genetics advances at breakneck speed, unraveling genetic mysteries via genom-ics, proteomics, and microarray analysis, we are at the cusp of the era of “personalized” medicine, by which knowledge of our unique genetic blueprint will allow us to anticipate, and hopefully obviate, a host of heritable diseases. The genetic aspects of thyroid diseases are manifest in all age groups, from the neonate with congenital hypothyroidism due to a newly defined mutation in thyroid hor-monogenesis, to the adult who is genetically predisposed to autoimmune thyroid disease because of aberrations of autoregulatory genes. The recognition of thyroid disease is of paramount importance, especially in the neonatal period. A failure to diagnose these diseases will have a profoundly adverse effect on the growth and development of the child. It is essential that practitioners are cognizant of how common thyroid diseases are in patients with certain genetic syndromes. Addressing these issues is essential for proper care. I recall seeing a patient with Down syndrome who was frequently treated for repeated bouts of secondarily infected num-mular eczema. Recognizing that approximately one-third of patients with Down syndrome have thyroid disorders, a thyroid-stimulating hormone (TSH) level was checked. The patient was found to be hypothyroid; once she was placed on thyroid hormone, the xerotic skin that predisposed her to developing eczema resolved, and secondary infection was no longer an issue. This chapter offers current insights into the pathogenesis and derma-tologic features of a host of chromosomal, mosaic, and inborn errors of metabolism that also affect the thyroid gland. When confronted with syndromal patients, thoughtful clinicians will entertain the possibility that there may be coexistent thyroid gland disorders and will research this by utilizing resources such as OMIM (the Online Mendelian Inheritance of Man database). It is a worthwhile endeavor to do so as maintaining a euthyroid state is crucial for optimal health.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kaye CI, Committee on Genetics. Newborn screening fact sheets. Pediatrics 2006;118:942–944.

    Article  Google Scholar 

  2. Avbelj M, Tahirovic H, Debeljak M, et al. High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis. Eur J Endocrinol 2007;156:511–519.

    Article  PubMed  CAS  Google Scholar 

  3. Park SM, Chatterjee VKK. Genetics of congenital hypothyroidism. J Med Genet 2005;42:379–389.

    Article  PubMed  CAS  Google Scholar 

  4. Moreno JC, Visser TJ. New phenotypes in thyroid dyshormonogenesis: hypothyroidism due to DUOX2 mutations. Endocr Dev 2007;10:99–117.

    Article  PubMed  CAS  Google Scholar 

  5. Zamproni I, Grasberger H, Cortinovis F, et al. Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. J Clin Endocrinol Metab 2007 Nov 27 [epub ahead of print].

    Google Scholar 

  6. van Tijn DA, Schroor EJ, Delemarre-van de Waal HA, de Vijlder JJ, Vulsma T. Early assessment of hypothalamic-pituitary-gonadal function in patients with congenital hypothyroidism of central origin. J Clin Endocrinol Metab 2007;92:104–109.

    Article  PubMed  CAS  Google Scholar 

  7. El Kholy M, Fahmi ME, Nassar AE, Selim S, Elsedfy HH. Prevalence of minor musculoskeletal anomalies in children with congenital hypothyroidism. Horm Res 2007;68:272–275.

    Article  CAS  Google Scholar 

  8. Kreisner E, Neto EC, Gross JL. High prevalence of extrathyroid malformations in a cohort of Brazilian patients with permanent primary congenital hypothy-roidism. Thyroid 2005;15:165–169.

    Article  PubMed  CAS  Google Scholar 

  9. Olivieri A, Stazi MA, Mastroiacovo P, et al, Study Group for Congenital Hypothyroidism. A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991–1998). J Clin Endocrinol Metab 2002;87:557–562.

    Article  PubMed  CAS  Google Scholar 

  10. Devos H, Rodd C, Gagné N, Laframboise R, Van Vliet G. A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations. J Clin Endocr Metab 1999;84:2502– 2506.

    Article  PubMed  CAS  Google Scholar 

  11. Stoll C, Dott B, Alembik Y, Koehl C. Congenital anomalies associated with congenital hypothy-roidism. Ann Genet 1999;42:17–20.

    PubMed  CAS  Google Scholar 

  12. Oakley GA, Muir T, Ray M, Girdwood RW, Kennedy R, Donaldson MD. Increased incidence of congenital malformations in children with transient thyroid-stimulating hormone elevation on neonatal screening. J Pediatr 1998;132:726–730.

    Article  PubMed  CAS  Google Scholar 

  13. Chao T, Wang JR, Hwang B. Congenital hypothy-roidism and concomitant anomalies. J Pediatr Endocrinol Metab 1997;10:217–221.

    Article  PubMed  CAS  Google Scholar 

  14. Siebner R, Merlob P, Kaiserman I, Sack J. Congenital anomalies concomitant with persistent primary congenital hypothyroidism. Am J Med Genet 1992;44:57–60.

    Article  PubMed  CAS  Google Scholar 

  15. Gruñeiro-Papendieck L, Chiesa A, Mendez V, Santilli A, Prieto L. Efficacy of congenital hypothy-roidism neonatal screening in preterms less than 32 weeks of gestational age: more evidence. J Pediatr Endocrinol Metab 2005;18:373–377.

    Article  PubMed  Google Scholar 

  16. Castanet M, Polak M, Bonaïïti-Pellié C, Lyonnet S, Czernichow P, Léger J. Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors. J Clin Endocrinol Metab 2001;86:2009–2014.

    Article  PubMed  CAS  Google Scholar 

  17. Castanet M, Polak M, Léger J. Familial forms of thyroid dysgenesis. Endocr Dev 2007;10:15–28.

    Article  PubMed  Google Scholar 

  18. De Felice M, Di Lauro R. Thyroid development and its disorders: genetics and molecular mechanisms. Endocr Rev 2004;25:722–746.

    Article  PubMed  CAS  Google Scholar 

  19. Camilot M, Teofoli F, Gandini A, et al. Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes. Clin Endocrinol (Oxf) 2005;63:146–151.

    Article  CAS  Google Scholar 

  20. Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 2004;74:168–175.

    Article  PubMed  CAS  Google Scholar 

  21. Zannini M, Avantaggiato V, Biffali E, et al. TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. EMBO J 1997:16:3185–3197.

    Article  PubMed  CAS  Google Scholar 

  22. Dathan N, Parlato R, Rosica A, De Felice M, Di Lauro R. Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair. Dev Dyn 2002;224:450–456.

    Article  PubMed  CAS  Google Scholar 

  23. Sequeira M, Al-Khafaji F, Park S, et al. Production and application of polyclonal antibody to human thyroid transcription factor 2 reveals thyroid transcription factor 2 protein expression in adult thyroid and hair follicles and prepubertal testis. Thyroid 2003;13:927–932.

    Article  PubMed  CAS  Google Scholar 

  24. Bamforth JS, Huges IA, Lazarus JH, Weaver CM, Harper PS. Congenital hypothyroidism, spiky hair, and cleft palate. J Med Genet 1989:26:49–60.

    Article  PubMed  CAS  Google Scholar 

  25. Clifton-Bligh RJ, Wentworth JM, Heinz P, et al. Mutation of the gene encoding human TTF-2 associ- ated with thyroid agenesis, cleft palate and choanal atresia. Nat Genet 1998;19:399–401.

    Article  PubMed  CAS  Google Scholar 

  26. Castanet M, Park SM, Smith A, et al. A novel loss-of function mutation in TTF2 is associated with congenital hypothyroidism, thyroid agenesis, and cleft palate. Hum Mol Genet 2002:11:2051–2159.

    Article  PubMed  CAS  Google Scholar 

  27. Baris I, Arisoy AE, Smith A, et al.. A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyre-osis. J Clin Endocrinol Metab 2006;91:4183–4187.

    Article  PubMed  CAS  Google Scholar 

  28. Carré A, Castanet M, Sura-Trueba S, et al. Polymorphic length of TTF2/FOXE1 alanine stretch: evidence for genetic susceptibility to thyroid dysgen-esis. Hum Genet 2007;122:467–476.

    Article  PubMed  CAS  Google Scholar 

  29. Santarpia L, Valenzise M, Di Pasquale G, et al. TTF-2/FOXE1 gene polymorphisms in Sicilian patients with permanent primary congenital hypothyroidism. J Endocrinol Invest 2007 30:13–19.

    PubMed  CAS  Google Scholar 

  30. Dentice M, Cordeddu V, Rosica A, et al. Missense mutation in the transcription factor NKX2-5:a novel molecular event in the pathogenesis of thyroid dys-genesis. J Clin Endocr Metab 2006;91:1428–1433.

    Article  PubMed  CAS  Google Scholar 

  31. Bakker B, Bikker H, Hennekam RCM, et al. Maternal isodisomy for chromosome 2p causing severe congenital hypothyroidism. J Clin Endocrinol Metab 2001:86:1164–1168.

    Article  PubMed  CAS  Google Scholar 

  32. Jabbour SA. Endocrinology in dermatology. Clin Dermatol 2006;24:235–236.

    Article  PubMed  Google Scholar 

  33. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991;325:1688–1695.

    Article  PubMed  CAS  Google Scholar 

  34. Schwindinger WF, Francomano CA, Levine MA. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G-protein of adeny-lyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci 1992;89:5152–5156.

    Article  PubMed  CAS  Google Scholar 

  35. Bhat MH, Bhadada S, Dutta P, Bhansali A, Mittal BR Hyperthyroidism with fibrous dysplasia: an unusual presentation of McCune-Albright syndrome. Exp Clin Endocrinol Diabetes 2007;115:331–333.

    Article  PubMed  CAS  Google Scholar 

  36. Lumbroso S, Paris F, Sultan C, European Collaborative Study. Activating Gs alpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome—a European Collaborative Study. J Clin Endocrinol Metab 2004;89:2107–2113.

    Article  PubMed  CAS  Google Scholar 

  37. Collins MT, Sarlis NJ, Merino MJ, et al. Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gs alpha mutations. J Clin Endocrinol Metab 2003;88:4413–4417.

    Article  PubMed  CAS  Google Scholar 

  38. Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000;26:89–92.

    Article  PubMed  CAS  Google Scholar 

  39. Wilson LC, Leverton K, Oude Luttikhuis C, et al. Brachydactyly and mental retardation: an Albright hereditary osteodystrophy-like syndrome localized to 2q37. Am J Hum Genet 1995;56:400–407.

    PubMed  CAS  Google Scholar 

  40. Liu J, Erlichman B, Weinstein LS. The stimulatory G protein alpha-subunit Gs-alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. J Clin Endocrinol Metab 2003;88:4336–4341.

    Article  PubMed  CAS  Google Scholar 

  41. Mantovani G, Bondioni S, Linglart A, et al. Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseu-dohypoparathyroidism type Ib. J Clin Endocrinol Metab 2007;9:3738–3742.

    Article  CAS  Google Scholar 

  42. Sheffield VC, Kraiem X, Beck JC, et al. Pendred syndrome maps to and is caused by an intrinsic defect in thyroid iodine organification. Nat Genet 1996;12:424–426.

    Article  PubMed  CAS  Google Scholar 

  43. Reardon W, Trembath RC. Pendred syndrome. J Med Genet 1996;33:1037–1040.

    Article  PubMed  CAS  Google Scholar 

  44. Bogazzi F, Russo D, Raggi F, et al. Mutations in the SLC26A4 (pendrin) gene in patients with sen-sorineural deafness and enlarged vestibular aqueduct. J Endocrinol Invest 2004;27:430–435.

    PubMed  CAS  Google Scholar 

  45. Banghova K, Taji EA, Cinek O, et al. Pendred syndrome among patients with congenital hypothy-roidism detected by neonatal screening: identification of two novel PDS/SLC26A4 mutations. Eur J Pediatr 2007 Sept 18 [epub ahead of print].

    Google Scholar 

  46. Gaudino R, Garel C, Czernichow P, Léger J. Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study. Clin Endocrinol 2005;62:444–448.

    Article  Google Scholar 

  47. Iwasaki S, Tsukamoto K, Usami S, Misawa K, Mizuta K, Mineta H. Association of SLC26A4 mutations with clinical features and thyroid function in deaf infants with enlarged vestibular aqueduct. J Hum Genet 2006;51:805–810.

    Article  PubMed  Google Scholar 

  48. Bidar J, Mian C, Lazar V, et al. Expression of pendrin and the Pendred syndrome (PDS) gene in human thyroid tissues. J Clin Endocrinol Metab 2000;85:2028–2033.

    Article  Google Scholar 

  49. Bashir EA, Ahmed S, Murtaza B, et al. Follicular carcinoma thyroid in Pendred syndrome. J Coll Physicians Surg Pak 2004;14:679–680.

    PubMed  Google Scholar 

  50. Skubis-Zegadlo J, Nikodemska A, Przytula E, et al. Expression of pendrin in benign and malignant human thyroid tissues. Br J Cancer 2005;93: 144–151.

    Article  PubMed  CAS  Google Scholar 

  51. Xing M, Tokumaru Y, Wu G, Westra WB, Ladenson PW, Sidransky D. Hypermethylation of the Pendred syndrome gene SLC26A4 may also be an early event in thyroid tumorigenesis. Cancer Res 2003;63:2312–2315.

    PubMed  CAS  Google Scholar 

  52. 52 Prasher VP. Down syndrome and thyroid disorders: a review. Downs Syndr Res Pract 1999;6:25–42

    Google Scholar 

  53. Thuline HC, Pueschel SM. Cytogenetics in Down syndrome. In: Pueschel SM, Rynders JE, eds. Down Syndrome. Advances in Biomedicine and the Behavioral Sciences. Cambridge, UK: Ware Press; 1982:133.

    Google Scholar 

  54. Hook EB Cross PK, Schreinemachers DM. Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA 1983;249:2034–2038.

    Article  PubMed  CAS  Google Scholar 

  55. Mikkelsen M. Down's syndrome cytogenetic epidemiology. Hereditas 1977;86:45–59.

    Article  PubMed  CAS  Google Scholar 

  56. Schepis C, Barone C, Siragusa M, Pettinato R, Romano C. An updated survey on skin conditions in Down syndrome. Dermatology 2002;205:234–238.

    Article  PubMed  Google Scholar 

  57. Ivarsson SA, Ericsson UB, Gustafsson J, Forslund M, Vegfors P, Annaren G. The impact of thyroid autoimmunity in children and adolescents with Down syndrome. Acta Paediatr 1997;86:1065–1067.

    Article  PubMed  CAS  Google Scholar 

  58. Reid AH, Adamson DG, Browning MC, Donald JM. A case of idiopathic Addison's disease and probable autoimmune thyroiditis in a mongol. J Ment Defic Res 1975;19:205–208.

    PubMed  CAS  Google Scholar 

  59. McCulloch AJ, Ince PG, Kendall-Taylor P. Autoimmune chronic active hepatitis in Down's syndrome. J Med Genet 1982;19:232–234.

    Article  PubMed  CAS  Google Scholar 

  60. Dinleyici EC, Ucar B, Kilic Z, Dogruel N, Yarar C. Pericardial effusion due to hypothyroidism in Down syndrome: report of four cases. Neuro Endocrinol Lett 2007;28:141–144.

    PubMed  Google Scholar 

  61. Tonacchera M, Perri A, De Marco G, et al. TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothy-roidism. J Endocrinol Invest 2003;26:997–1000.

    PubMed  CAS  Google Scholar 

  62. Gruñeiro de Papendieck L, Chiesa A, et al. Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome. J Pediatr Endocrinol Metab 2002;15:1543–1548.

    Article  PubMed  Google Scholar 

  63. van Trotsenburg AS, Vulsma T, van Rozenburg-Marres SL, et al. The effect of thyroxine treatment started in the neonatal period on development and growth of 2-year-old Down syndrome children: a randomized clinical trial. J Clin Endocrinol Metab 2005;90:3304–3311.

    Article  PubMed  CAS  Google Scholar 

  64. Tüüysüz B, Beker DB Thyroid dysfunction in children with Down's syndrome. Acta Paediatr 2001;90: 1389–1393.

    Article  Google Scholar 

  65. Hasanhodzić M, Tahirović H, Lukinac L. Down Syndrome and thyroid gland. Bosn J Basic Med Sci 2006;6:38–42.

    PubMed  Google Scholar 

  66. Gibson PA, Newton RW, Selby K, Price DA, Leyland K, Addison GM. Longitudinal study of thyroid function in Down's syndrome in the first two decades. Arch Dis Child 2005;90:574–578.

    Article  PubMed  CAS  Google Scholar 

  67. Oliveira AT, Longui CA, Calliari EP, Ferone Ede A, Kawaguti FS, Monte O. [Evaluation of the hypotha-lamic-pituitary-thyroid axis in children with Down syndrome]. J Pediatr (Rio J) 2002;78:295–300.

    Google Scholar 

  68. van Trotsenburg AS, Vulsma T, van Santen HM, Cheung W, de Vijlder JJ. Lower neonatal screening thyroxine concentrations in down syndrome new-borns. J Clin Endocrinol Metab 2003;88:1512–1515.

    Article  PubMed  CAS  Google Scholar 

  69. Konings CH, van Trotsenburg AS, Ris-Stalpers C, Vulsma T, Wiedijk BM, de Vijlder JJ. Plasma thy-rotropin bioactivity in Down's syndrome children with subclinical hypothyroidism. Eur J Endocrinol 2001;144:1–4.

    Article  PubMed  CAS  Google Scholar 

  70. van Trotsenburg AS, Kempers MJ, Endert E, Tijssen JG, de Vijlder JJ, Vulsma T. Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin. Thyroid 2006;16:671–680.

    Article  PubMed  Google Scholar 

  71. Caraccio N, Dardano A, Manfredonia F, et al. Longterm follow-up of 106 multiple sclerosis patients undergoing interferon-{beta} 1a or 1b therapy: predictive factors of thyroid disease development and duration. J Clin Endocrinol Metab 2005;90: 4133–4137.

    Article  PubMed  CAS  Google Scholar 

  72. American Academy of Pediatrics, Committee on Genetics. American Academy of Pediatrics: health supervision for children with Down syndrome. Pediatrics 2001;107:442–449.

    Article  Google Scholar 

  73. Dias VM, Nunes JC, Araújo SS, Goulart EM. [Etiological assessment of hyperthyrotropinemia in children with Down's syndrome]. J Pediatr (Rio J) 2005;81:79–84.

    Google Scholar 

  74. Mathis D, Benoist C. A decade of AIRE. Nat Rev Immunol 2007;7:645–650.

    Article  PubMed  CAS  Google Scholar 

  75. Söderbergh A, Gustafsson J, Ekwall O, et al. Autoantibodies linked to autoimmune polyendocrine syndrome type I are prevalent in Down syndrome. Acta Paediatr 2006;95:1657–1660.

    Article  PubMed  Google Scholar 

  76. Livadas S, Xekouki P, Fouka F, et al. Prevalence of thyroid dysfunction in Turner's syndrome: a long-term follow-up study and brief literature review. Thyroid 2005;15:1061–1066.

    Article  PubMed  CAS  Google Scholar 

  77. Auada MP, Cintra ML, Puzzi MB, Viana D, Cavalcanti DP. Scalp lesions in Turner syndrome: a result of lymphoedema? Clin Dysmorphol 2004;13:165–168.

    Article  PubMed  Google Scholar 

  78. Dacou-Voutetakis C, Kakourou T. Psoriasis and blue sclerae in girls with Turner syndrome. J Am Acad Dermatol 1996;35:1002–1004.

    Article  PubMed  CAS  Google Scholar 

  79. Watabe H, Kawakami T, Kimura S, Fujimoto M, et al. Childhood psoriasis associated with Turner syndrome. J Dermatol 2006;33:896–898.

    Article  PubMed  Google Scholar 

  80. Rosina P, Segalla G, Magnanini M, Chieregato C, Barba A. Turner syndrome associated with psoriasis and alopecia areata. J Eur Acad Dermatol Venereol 2003;17:50–52.

    Article  PubMed  CAS  Google Scholar 

  81. Atria A, Sanz R, Donoso S. Necropsy study of a case of Turner's síndrome. Case report. J Clin Endocrin Metab 1948;8:397–405.

    Article  CAS  Google Scholar 

  82. El-Mansoury M, Bryman I, Berntorp K, Hanson C, Wilhelmsen L, Landin-Wilhelmsen K. Hypothyroidism is common in Turner syndrome: results of a 5-year follow-up. J Clin Endocrinol Metab 2005;90:2131–2135.

    Article  PubMed  CAS  Google Scholar 

  83. Radetti G, Mazzanti L, Paganini C, et al. Frequency, clinical and laboratory features of thyroiditis in girls with Turner's syndrome. The Italian Study Group for Turner's Syndrome. Acta Paediatr 1995;84: 909–912.

    Article  PubMed  CAS  Google Scholar 

  84. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a 20-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55–68.

    Article  CAS  Google Scholar 

  85. Elsheikh M, Wass JA, Conway GS. Autoimmune thyroid syndrome in women with Turner's syndrome—the association with karyotype. Clin Endocrin 2001;55:223–226.

    Article  CAS  Google Scholar 

  86. Susperreguy S, Miras MB, Montesinos MM, et al. Growth hormone (GH) treatment reduces peripheral thyroid hormone action in girls with Turner syndrome. Clin Endocrinol (Oxf) 2007;67:629–636.

    CAS  Google Scholar 

  87. Festen DA, Visser TJ, Otten BJ, Wit JM, Duivenvoorden HJ, Hokken-Koelega AC. Thyroid hormone levels in children with Prader-Willi syndrome before and during growth hormone treatment. Clin Endocrinol (Oxf) 2007;67:449–456.

    Article  CAS  Google Scholar 

  88. Cabanas P, García-Caballero T, Barreiro J, et al. Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome. Eur J Endocrinol 2005;153:499–502.

    Article  PubMed  CAS  Google Scholar 

  89. Tita P, Ambrosio MR, Scollo C. High prevalence of differentiated thyroid carcinoma in acromegaly. Clin Endocrinol (Oxf) 2005;63:161–167.

    Article  Google Scholar 

  90. Mass E, Belostoky L. Craniofacial morphology of children with Williams syndrome. Cleft Palate Craniofac J 1993;30:343–349.

    Article  PubMed  CAS  Google Scholar 

  91. Preus M. The Williams syndrome: objective definition and diagnosis. Clin Genet 1984;25:422–428.

    Article  PubMed  CAS  Google Scholar 

  92. Holmström G, Almond G, Temple K, Taylor D, Baraitser M. The iris in Williams syndrome. Arch Dis Child 1990;65:987–989.

    Article  PubMed  Google Scholar 

  93. Winter M, Pankau R, Amm M, Gosch A, Wessel A. The spectrum of ocular features in the Williams-Beuren syndrome. Clin Genet 1996;49:28–31.

    Article  PubMed  CAS  Google Scholar 

  94. Gosch A, Städing G, Pankau R. Linguistic abilities in children with Williams-Beuren syndrome. Am J Med Genet 1994;1;52:291–296.

    Article  PubMed  CAS  Google Scholar 

  95. Cherniske EM, Carpenter TO, Klaiman C, et al. Multisystem study of 20 older adults with Williams syndrome. Am J Med Genet A 2004;131:255–264.

    Article  PubMed  Google Scholar 

  96. Culler FL, Jones KL, Deftos LJ. Impaired calci-tonin secretion in patients with Williams syndrome. J Pediatr 1985;107:720–723.

    Article  PubMed  CAS  Google Scholar 

  97. Committee on Genetics. American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Pediatrics 2007;107:1192–1204.

    Google Scholar 

  98. Cammareri V, Vignati G, Nocera G, Beck-Peccoz P, Persani L. Thyroid hemiagenesis and elevated thy-rotropin levels in a child with Williams syndrome. Am J Med Genet 1999;85:491–494.

    Article  PubMed  CAS  Google Scholar 

  99. Stagi S, Bindi G, Neri AS, et al. Thyroid hypoplasia of the left lobe in two girls affected by Williams syndrome. Clin Dysmorphol 2003;12:267–268.

    Article  PubMed  Google Scholar 

  100. Bini R, Pela I. New case of thyroid dysgenesis and clinical signs of hypothyroidism in Williams syndrome. Am J Med Genet A 2004;127:183–185.

    Article  Google Scholar 

  101. Cappa M, Galasso C, Boscherini B. Aspetti auxo-logici ed endocrinologici. In: Giannotti A, Vicari S eds. Il bambino con sindrome di Williams. Milan: Franco Angeli; 1994:59–64.

    Google Scholar 

  102. Selicorni A, Fratoni A, Pavesi MA, Bottigelli M, Arnaboldi E, Milani D. Thyroid anomalies in Williams syndrome: investigation of 95 patients. Am J Med Genet A 2006;140:1098–1101.

    PubMed  CAS  Google Scholar 

  103. Stagi S, Bindi G, Neri AS, et al. Thyroid function and morphology in patients affected by Williams syndrome. Clin Endocrinol (Oxf) 2005;63:456–460.

    Article  Google Scholar 

  104. Cambiaso P, Orazi C, Digilio MC, et al. Thyroid morphology and subclinical hypothyroidism in children and adolescents with Williams syndrome. J Pediatr 2007;150:62–65.

    Article  PubMed  Google Scholar 

  105. Ghomrasseni S, Dridi M, Bonnefoix M, et al. Morphometric analysis of elastic skin fibres from patients with: cutis laxa, anetoderma, pseudox-anthoma elasticum, and Buschke-Ollendorff and Williams-Beuren syndromes. J Eur Acad Dermatol Venereol 2001;15:305–311.

    PubMed  CAS  Google Scholar 

  106. Urbán Z, Peyrol S, Plauchu H, et al. Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibers in skin and a subclinical dermal phenotype. Pediatr Dermatol 2000;17:12–20.

    Article  PubMed  Google Scholar 

  107. Dridi SM, Ghomrasseni S, Bonnet D, et al. Skin elastic fibers in Williams syndrome. Am J Med Genet 1999;87:134–138.

    Article  PubMed  CAS  Google Scholar 

  108. Matsuoka LY, Wortsman J, Uitto J, et al. Altered skin elastic fibers in hypothyroid myxedema and pretibial myxedema. Arch Intern Med 1985;145:117–121.

    Article  PubMed  CAS  Google Scholar 

  109. Yamagishi H. The 22q11.2 deletion syndrome. Keio J Med 2002;51:77–88.

    Article  PubMed  CAS  Google Scholar 

  110. Hutson MR, Kirby ML. Model systems for the study of heart development and disease. Cardiac neural crest and conotruncal malformations. Semin Cell Dev Biol. 2007;18:101–110.

    Article  PubMed  CAS  Google Scholar 

  111. McDonald-McGinn DM, Emanuel BS, Zackai EH. 22q11.2 deletion syndrome. Updated December 16, 2005. In: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle. 1997–2007. Available at: http://www.genetests.org. Accessed December 9, 2007.

  112. Kobrynski LJ, Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 2007;370(9596):1443–1452.

    Article  PubMed  CAS  Google Scholar 

  113. Bassett AS, Chow EW, Husted J, et al. Clinical features of 78 adults with 22q11 deletion syndrome. Am J Med Genet A 2005;138:307–313.

    PubMed  Google Scholar 

  114. Choi JH, Shin YL, Kim GH, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res 2005;63:294–299.

    Article  PubMed  CAS  Google Scholar 

  115. Weinzimer SA. Endocrine aspects of the 22q11.2 deletion syndrome. Genet Med 2001;3:19–22.

    Article  PubMed  CAS  Google Scholar 

  116. Kitsiou-Tzeli S, Kolialexi A, Mavrou A. Endocrine manifestations in DiGeorge and other microdeletions related to 22q11.2. Hormones 2005;4:200–209.

    PubMed  Google Scholar 

  117. Greig F, Paul E, DiMartino-Nardi J, Saenger P. Transient congenital hypoparathyroidism: resolution and recurrence in Chromosome 22q11 deletion. J Pediatr 1996;128:563–567.

    Article  PubMed  CAS  Google Scholar 

  118. Cuneo BF, Driscoll DA, Gidding SS, Langman CB. Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome. Am J Med Genet 1997;69:50–55.

    Article  PubMed  CAS  Google Scholar 

  119. Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 2001;139:715–723.

    Article  PubMed  CAS  Google Scholar 

  120. McLean-Tooke A, Spickett GP, Gennery AR. Immunodeficiency and autoimmunity in 22q11.2 deletion syndrome. Scand J Immunol 2007;66:1–7.

    Article  PubMed  CAS  Google Scholar 

  121. Kawamura T, Nimura I, Hanafusa M, et al. DiGeorge syndrome with Graves' disease: a case report. Endocr J 2000;47:91–95.

    Article  PubMed  CAS  Google Scholar 

  122. Kawame H, Adachi M, Tachibana K, et al. Graves' disease in patients with 22q11.2 deletion. J Pediatr 2001;139:892–895.

    Article  PubMed  CAS  Google Scholar 

  123. Brown JJ, Datta V, Browning MJ, Swift PG. Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion. J Pediatr Endocrinol Metab 2004;17:1575–1579.

    Article  PubMed  CAS  Google Scholar 

  124. Liao J, Kochilas L, Nowotschin S, et al. Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage. Hum Mol Genet 2004;13:1577–1585.

    Article  PubMed  CAS  Google Scholar 

  125. Zweier C, Sticht H, Aydin-Yaylagül I, Campbell CE, Rauch A. Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions. Am J Hum Genet 2007;80:510–517.

    Article  PubMed  CAS  Google Scholar 

  126. Lindsay EA, Vitelli F, Su H, Morishima M, et al. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 2001;410:97–101.

    Article  PubMed  CAS  Google Scholar 

  127. Baldini A. Dissecting contiguous gene defects: TBX1. Curr Opin Genet Dev 2005;15:79–284.

    Article  CAS  Google Scholar 

  128. Fagman H, Liao J, Westerlund J, Andersson L, Morrow BE, Nilsson M. The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning. Hum Mol Genet 2007;16:276–285.

    Article  PubMed  CAS  Google Scholar 

  129. Fagman H, Anderson L, Nilsson M. The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specifica- tion, budding, migration, and lobulation. Dev Dyn 2006;235:444–455.

    Article  PubMed  CAS  Google Scholar 

  130. Palacios J, Gamallo C, García M, Rodríguez JI. Decrease in thyrocalcitonin-containing cells and analysis of other congenital anomalies in 11 patients with DiGeorge anomaly. Am J Med Genet 1993;46:641–646.

    Article  PubMed  CAS  Google Scholar 

  131. Pueblitz S, Weinberg AG, Albores-Saavedra J. Thyroid C cells in the DiGeorge anomaly: a quantitative study. Pediatr Pathol 1993;13: 463–473.

    Article  PubMed  CAS  Google Scholar 

  132. Scuccimarri R, Rodd C. Thyroid abnormalities as a feature of DiGeorge syndrome: a patient report and review of the literature. J Pediatr Endocrinol 1998;11:273–276.

    Article  CAS  Google Scholar 

  133. Preece JM, Smith RA. Thyroid disease in children with 22q11.2 deletion syndrome. J Pediatr 2002;141:297.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Dermatology, Cooper University Hospital, Camden, NJ, USA

    Analisa V. Halpern MD

  2. Department of Pediatrics, Cooper University Hospital, Camden, NJ, USA

    Rhonda E. Schnur

Authors
  1. Analisa V. Halpern MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rhonda E. Schnur
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School at Camden, Marlton, NJ, USA

    Warren R. Heymann MD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag London Limited

About this chapter

Cite this chapter

Halpern, A.V., Schnur, R.E. (2008). Chromosomes, Genes, and the Thyroid Gland. In: Heymann, W.R. (eds) Thyroid Disorders with Cutaneous Manifestations. Springer, London. https://doi.org/10.1007/978-1-84800-187-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-84800-187-9_7

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84800-186-2

  • Online ISBN: 978-1-84800-187-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation